BRD4 is involved in viral exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD. METHODS: BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant. RESULTS: BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression. CONCLUSIONS: Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.

Nurse-Led Motor Function Rehabilitation Program for Acute Ischemic Stroke: A Randomized Pilot Study.

BACKGROUND: Rehabilitation care for patients with stroke in the acute stage must be strengthened. However, the evidence on how to strengthen this care is insufficient. PURPOSE: This article was designed to evaluate the feasibility and effectiveness of implementing a nurse-led motor function rehabilitation program on patients with acute ischemic stroke. METHODS: From January to October 2018, patients with initial acute ischemic stroke were assigned to one of two groups using a pilot randomized controlled trial design, with one group receiving a nurse-led motor function intervention program developed based on Orem's theory (7 consecutive days, twice daily for 30 minutes, experimental group) and the other receiving usual care (control group). The effectiveness measures included changes in the Motor Assessment Scale, the modified Barthel Index, and the National Institutes of Health Stroke Scale. The feasibility measures included patient retention rate, incidence of adverse events, and acceptance of nurses and patients. RESULTS: We assigned 104 patients (male: 55.7%; age: 62.8 ± 13.2 years) to receive either a nurse-led motor function rehabilitation program or usual care. Eighty-eight patients were evaluated after 7 days (87% retention rate), including 43 (83% retention rate) in the experimental group. Patients accepted the intervention well, and no severe adverse events were reported. Nurses had good fidelity and showed high acceptance. The experimental group showed significantly higher postintervention Motor Assessment Scale and modified Barthel Index scores than the control group (p < .001), whereas postintervention National Institutes of Health Stroke Scale scores did not differ significantly between the two groups. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The nurse-led rehabilitation program used in this study was shown to be feasible and effective in improving motor function in patients with acute ischemic stroke. Further study is recommended to determine related clinical recommendations.

Increased CAP37 Expression in Stable Chronic Obstructive Pulmonary Disease.

OBJECTIVE: Cationic antimicrobial protein of 37 kDa (CAP37), a neutrophil-derived protein originally identified for its antimicrobial activity, is now known to have many regulatory effects on host cells. However, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) has not been studied. We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells, including bronchial epithelial cells, smooth muscle cells, and fibroblasts. METHODS: CAP37 was detected in the lung tissue, sputum, and plasma of COPD patients and the control subjects, as well as in the neutrophils stimulated by cigarette smoke extract (CSE). BEAS-2B cells, human bronchial smooth muscle cells (HBSMCs), and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37. Interleukin (IL)-6 and IL-8 were detected in the BEAS-2B cells. The cell proliferation was analyzed in the HBSMCs. Collagens were also detected in the MRC-5 cells. RESULTS: The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects. The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD. CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers. CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells, and collagen expression of lung fibroblasts (MRC-5 cells). However, CAP37 did not significantly alter the proliferation of the HBSMCs. CONCLUSION: Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells, and fibroblasts, thus suggesting a possible role of CAP37 in the development and progression of COPD.

Comparison of LAMP, GeneXpert, Mycobacterial Culture, Smear Microscopy, TSPOT.TB, TBAg/PHA Ratio for Diagnosis of Pulmonary Tuberculosis.

OBJECTIVE: To investigate the application value of loop-mediated isothermal amplification (LAMP), GeneXpert, mycobacterial culture, smear microscopy, TSPOT.TB (TSPOT), ratio of TB-specific antigen to phytohemagglutinin (TBAg/PHA ratio) in the detection of mycobacterium tuberculosis in the bronchoalveolar lavage fluid. METHODS: A retrospective analysis was performed on the patients who underwent bronchoscopy from December 2018 to November 2019 in Tongji Hospital. The patients with positive tuberculosis culture or positive GeneXpert in bronchoalveolar lavage fluid were selected as the case group, and those without tuberculosis served as the control group. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of LAMP, GeneXpert, culture, smear microscopy, TSPOT, and TBAg/PHA ratio. RESULTS: For the patients with positive cultures as case, the sensitivity of LAMP, GeneXpert, smear microscopy, TSPOT and TBAg/PHA ratio was 73.49%, 89.16%, 25.30%, 80.00%, 33.85%, respectively, the specificity was 99.00%, 100.00%, 99.00%, 86.00%, 100.00%, respectively, the area under the ROC curve (AUC) was 0.849, 0.938, 0.633, 0.830, 0.669, respectively. For the patients with positive GeneXpert as case, the sensitivity of LAMP, mycobacterial culture, smear microscopy, TSPOT and TBAg/PHA ratio was 73.20%, 74.23%, 22.68%, 68.92%, 29.73%, respectively, the specificity was 99.00%, 100.00%, 99.00%, 86.00%, 100.00%, respectively, the AUC was 0.853, 0.878, 0.623, 0.775, 0.649, respectively. CONCLUSION: The sensitivity of GeneXpert was best. The sensitivity and diagnostic value of LAMP were slightly lower than those of GeneXpert, and were similar to tuberculosis culture. The sensitivity of smear microscopy was low. The specificity of TSPOT was low. When TBAg/PHA ratio >0.2 was used as a diagnostic index, the specificity was improved, but the sensitivity was low.

Evaluation of Blood Markers at Admission for Predicting Community Acquired Pneumonia in Chronic Obstructive Pulmonary Disease.

Acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) and community acquired pneumonia (CAP) are two common acute attacks in COPD patients and it is not always easy to determine whether a COPD patient at admission has parenchymal infection or bronchial infection. Comprehensive comparison between AECOPD patients and CAP patients with COPD (COPD + CAP) can help us understand them better. We retrospectively collected the medical records of AECOPD and COPD + CAP patients. Systemic inflammation, eosinophilic inflammation, damage to other organs, common chronic comorbidities, structural changes, phenotype and endotype distributions and coagulation functions between two groups were compared and correlations of these characteristics in total subjects, AECOPD patients and COPD + CAP patients were analyzed. Logistic regression analysis was performed to select helpful biomarkers for distinguishing between them. Receiver operator characteristic (ROC) curve was plotted to assess the diagnostic value of selected biomarkers and their combination. A nomogram was established for the differential diagnosis of AECOPD and COPD + CAP. A total of 206 patients were included into our analysis. In these subjects, 104 patients were classified as AECOPD group and 102 patients were considered to have COPD + CAP mainly based on their chest CT scan results. The counts of eosinophils (EOS), basophils (BAS) and lymphocytes (LYM) and percentage of total white blood cell count, hemoglobin and hematocrit were increased in AECOPD patients compared with COPD + CAP patients. The counts of neutrophils (NEU) and percentage of total white blood cell count, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), fibrinogen, D-dimer and N-Terminal pro-brain natriuretic peptide (NT-proBNP) levels were increased in COPD + CAP patients. After logistic regression analysis, EOS < 0.5 × 109/L, ESR ≥ 8 mm/H and NT-proBNP ≥ 100 pg/mL were selected as helpful biomarkers for diagnosis of COPD + CAP instead of AECOPD. Area under the ROC curve (AUC) of the combination of selected biomarkers was 0.764(0.698-0.829). A nomogram was established and the calibration curve suggested that fitting efficiency of the nomogram was good. AECOPD and COPD + CAP are markedly different, mainly reflected in eosinophilic inflammation, systemic inflammation and coagulation function. Correlations between some common inflammatory biomarkers are also different in the two groups. A nomogram was established to offer help to clinicians for differential diagnosis of these two diseases.

Effectiveness of Rehabilitation Nursing versus Usual Therapist-Led Treatment in Patients with Acute Ischemic Stroke: A Randomized Non-Inferiority Trial.

PURPOSE: To determine the effectiveness of rehabilitation nursing program interventions in patients with acute ischemic stroke. PATIENTS AND METHODS: An assessment-blinded randomized controlled trial was conducted at a tertiary referral hospital in China. Eligible patients were stratified according to their weighted corticospinal tract lesion load and then randomly assigned to an experimental group (n = 121) or a control group (n = 103). The experimental group received rehabilitation nursing from well-trained, qualified nurses (30 minutes per session, two sessions per day for seven consecutive days). The control group received therapist-led rehabilitation with the same timing and frequency. Comparative analysis of the primary outcomes was performed to determine non-inferiority with a predetermined non-inferiority margin. The primary outcomes were the Motor Assessment Scale, Fugl-Meyer Assessment, and the Action Research Arm Test assessed at baseline and after seven days of treatment. The secondary outcomes were the modified Barthel Index, the National Institutes of Health Stroke Scale, and the modified Rankin Scale, evaluated before and after the intervention and at 4 and 12 weeks of follow-up. RESULTS: Two hundred participants completed the trial. In both groups, all outcomes improved significantly after seven days and at follow-ups. The rehabilitation nursing program was non-inferior to therapist-led treatment with lower 95% confidence limits beyond the margins for primary outcomes (P < 0.001). CONCLUSION: Both treatments had comparable effects; however, no definite conclusion could be drawn. Adequately powered studies are required.

Activities of daily living measurement after ischemic stroke: Rasch analysis of the modified Barthel Index.

ABSTRACT: In patients with ischemic stroke, activities of daily living were used as an outcome indicator, and correct assessment is very important. We sought to examine the reliability and validity of the modified Barthel Index as an evaluation tool of activities of daily living in ischemic stroke patients by applying the Rasch analysis.We used a prospectively collected cohort of ischemic stroke patients in the department of neurology. Rasch analysis was used for evaluating the reliability and validity of the modified Barthel Index.A total of 231 patients were included in the analysis. The average of modified Barthel Index was 36.2 ±â€Š17.8. The modified Barthel Index had high reliability of 0.88. There were no extremely mismatched items, and considered unidimensional, but the Point-Measure of bowels and bladder were 0.27, extremely lower than other items. The scale was stable in different sex and age, but had notable differential item functioning in muscle strength of the limbs. Rating categories were not functioning adequately in items. The item difficulty and patient ability were not matched, with a difference of 1.17 logics. 29.4% patients, no easy items could match their ability.The modified Barthel Index had high reliability but a relatively bad matching degree between item difficulty and patient ability. It still needs further improvement to reflect the activities of daily living in ischemic stroke patients.

The single nucleotide polymorphisms of interleukin-10 are associated with the risk of leukaemia: Evidence from 18 case-control studies.

Interleukin-10(IL-10) is an immunosuppressive cytokine and plays an important role in inflammation and cancers. Numerous studies have explored the association between single nucleotide polymorphisms of IL-10 and leukemia, but their results were conflicting, so we performed this meta-analysis to elucidate the association between 3 common single nucleotide polymorphisms of IL-10 (rs1800896, rs1800871 and rs1800872) and risk of leukemia.We conducted a comprehensive research in Pubmed, Chinese Biomedical Literature Database disc and Embase using related terms. After strict selection, 18 studies with 2264 cases and 3846 controls were included into this meta-analysis. Odds ratio and 95% confidence interval were used to evaluate the strength of the association.We found that polymorphism of IL-10 -1082A/G was associated with decreased risk of leukemia both in overall analysis and in stratified analysis according to ethnicity and cancer type. A strong relationship was also uncovered between polymorphism of IL-10 -592C/A and increased risk of leukemia in non-Chinese.GG genotype of IL-10 -1082A/G is associated with decreased risk of leukemia, especially chronic lymphocytic leukemia. CC genotype of -592C/A is associated with decreased risk of leukemia in non-Chinese.

Pentraxin 3 promotes airway inflammation in experimental asthma.

BACKGROUND: Pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation. Recently, it has been reported that PTX3 deficiency enhances interleukin (IL)-17A-dominant pulmonary inflammation in an ovalbumin (OVA)-induced mouse asthma model. However, whether PTX3 treatment would provide protection against allergic airway inflammation has not been clearly elucidated. The goal of this study was to further investigate the effect of recombinant PTX3 administration on the phenotype of asthma. METHODS: C57BL/6 J mice were sensitized and challenged with OVA to induce eosinophilic asthma model, as well as sensitized with OVA plus LPS and challenged with OVA to induce neutrophilic asthma model. We evaluated effect of recombinant PTX3 on asthma phenotype through both asthma models. The bronchoalveolar lavage fluid (BALF) inflammatory cells and cytokines, airway hyperresponsiveness, and pathological alterations of the lung tissues were assessed. RESULTS: In both eosinophilic and neutrophilic asthma models, PTX3 treatment provoked airway hyperresponsiveness, concomitant with increased inflammatory cytokines IL-4, IL-17, eotaxin, and transforming growth factor (TGF)-ß1 and aggravated airway accumulation of inflammatory cells, especially eosinophils and neutrophils. In histological analysis of the lung tissue, administration of PTX3 promoted inflammatory cells infiltration, mucus production, and collagen deposition. In addition, PTX3 also significantly enhanced STAT3 phosphorylation in lung tissue. CONCLUSION: Our results show that exogenous PTX3 can exacerbate multiple asthmatic features by promoting both eosinophils and neutrophils lung infiltration and provide new evidence to better understand the complex role of PTX3 in allergic airway inflammation.

Rehabilitation nursing for motor functional recovery of acute ischaemic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Stroke is the second-leading cause of death and disability in the world, and patients with stroke often suffer from functional impairments and need rehabilitation. Notably, there is much evidence that rehabilitation can lead to better mortality and morbidity outcomes. The evidence for the effectiveness of rehabilitation nursing, however, is limited. Thus, this study seeks to explore whether rehabilitation nursing is not inferior to usual rehabilitation for motor functional recovery in patients with acute ischaemic stroke. METHODS AND ANALYSIS: We will conduct an assessor-blinded parallel randomised controlled trial of patients who meet the inclusion criteria after stratification by weighted corticospinal tract lesion load. The experimental group will receive rehabilitation nursing by trained and qualified nurses (seven consecutive days, two sessions per day, 30 min each session). The control group will receive usual rehabilitation provided by therapists (seven consecutive days, two sessions per day, 30 min each session). The primary outcome measures are the Motor Assessment Scale, the Fugl-Meyer Assessment and the Action Research Arm Test. The secondary outcome measures are the modified Rankin Scale, the modified Barthel Index and the National Institute of Health Stroke Scale. Primary and secondary outcome assessment will be performed before and after the intervention, and secondary outcome be assessed at 4 and 12 weeks follow-up. We will recruit 224 patients within a period of 12-18 months from a hospital in southeastern China. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee from the corresponding author's hospital (approval Number is Ethical Review Study No. 2018 - 112). Peer-reviewed journals and presentations at national and international conferences will be used to disseminate the results. TRIAL REGISTRATION NUMBER: NCT03702452.

5-HT7 Receptor Contributes to Proliferation, Migration and Invasion in NSCLC Cells.

INTRODUCTION: Because only a small portion of NSCLC (non-small-cell lung cancer) patients benefit from molecular targeted therapy or immunotherapy and do not develop therapeutic resistance, continued research on new targets is warranted. Serotonin has recently emerged as a growth factor for tumor cells, and its receptors may be potential therapeutic targets. The mechanism related to the behavior of the 5-HT7 receptor in NSCLC remains unknown. METHODS: Both gene expression analysis and immunohistochemical analysis were conducted to evaluate 5-HT7 receptor expression in NSCLC tissues. The correlation between 5-HT7 receptor expression and clinicopathological features was also examined. Cell proliferation was measured using a CCK8 (Cell Counting Kit-8) assay and colony formation, migration and invasion were evaluated by the Transwell assay. siRNA transfection and stimulation with the selective agonist LP211 were used to identify the involvement of molecules in proliferation, migration and invasion. Quantitative real-time chain reaction (qRT-PCR) and Western blotting were used to quantifiy mRNA and protein levels, respectively. Pathway inhibitors facilitated the exploration of possible signaling pathways regulated by the 5-HT7 receptor in migration and invasion. RESULTS: The 5-HT7 receptor was overexpressed in NSCLC tumor tissues compared with adjacent normal lung tissues. High 5-HT7 receptor expression levels were correlated with lymph node metastasis (P=0.007) and advanced TNM stage (P=0.000) in NSCLC patients. The 5-HT7 receptor positively regulated cell proliferation, migration and invasion in NSCLC cells. The stimulatory effect of the 5-HT7 receptor on A549 cell migration and invasion may occur through the P38 pathway. In H1299 cells, the 5-HT7 receptor might positively regulate Src to promote cell migration and invasion. CONCLUSION: Our findings suggest that the 5-HT7 receptor, which mediates NSCLC progression, may be a potential therapeutic target.

The effects of BAFF on T lymphocytes in chronic obstructive pulmonary disease.

BACKGROUND: It has been reported that B cell activating factor belonging to the tumor necrosis factor family (BAFF) expression is increased in chronic obstructive pulmonary disease (COPD). However its role in this chronic inflammatory disease is not fully understood. Previous studies have suggested that BAFF also affects T cell function. We therefore investigated the effects of BAFF on T lymphocytes in COPD. METHODS: BAFF was detected in the cells of sputum and the plasma. Peripheral blood mononuclear cells (PBMCs) were isolated from COPD patients and treated with BAFF or BAFF plus BR3-Fc (BAFF antagonist). The apoptosis of CD4+ cells and CD8+ cells was analyzed by flow cytometry. CD4+ cells and CD8+ cells were isolated from peripheral blood of COPD patients respectively and treated with BAFF or BAFF plus BR3-Fc. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected in the CD4+ cells, and perforin and granzyme B were detected in the CD8+ cells. RESULTS: BAFF expression was increased in the cells of sputum and the plasma from COPD patients compared with control subjects. The plasma BAFF levels were inversely correlated with FEV1 percentage of predicted in patients with COPD. BAFF did not significantly alter the apoptosis of CD4+ cells, however it significantly inhibited the apoptosis of CD8+ cells from COPD patients. BAFF increased IFN-γ expression in the CD4+ cells from COPD patients, while it did not significantly alter the expresson of IL-4 in these cells. BAFF increased the expression of perforin and granzyme B in the CD8+ cells from COPD patients. CONCLUSIONS: Our findings indicate that BAFF may be involved in the inflammatory response in COPD via affecting T lymphocytes, suggesting a possible role of BAFF in the pathogenesis of COPD.

A hospital-wide reduction in central line-associated bloodstream infections through systematic quality improvement initiative and multidisciplinary teamwork.

BACKGROUND: Few data are available on hospital-wide incidence of central line-associated bloodstream infection (CLABSI) rates in patients with central venous catheter (CVC) in China, where many systemic obstacles holding back evidence-based guidelines implementation exist. METHODS: This study was conducted prospectively in 2 phases. The baseline and intervention phases were performed in a teaching hospital in China, between January 2017 and October 2018. A systematic quality improvement (SQI) and multidisciplinary teamwork (MDT) CLABSI infection control program was introduced in the intervention phase. In the intensive care units (ICUs) and non-ICUs, CLABSIs were continuously monitored, data collected, then analyzed. RESULTS: After intervention, the CLABSI rate decreased from 2.84-0.56 per 1,000 CVC days in ICUs (P < .001), and from 0.82-0.47 per 1,000 CVC days in non-ICUs (P = .003). The length of time until CLABSI occurrence increased from 8.72-13.60 days in ICUs (P = .046), and from 10.00-12.00 days in non-ICUs (P = .048). The number of multidrug-resistant bacteria isolated from CLABSI episodes decreased both in ICUs and in non-ICUs. CONCLUSIONS: The SQI and MDT CLABSI infection control program is effective in reducing hospital-wide CLABSI in patients with CVC, both in ICUs and in non-ICUs.

Decreased miR-29b expression is associated with airway inflammation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common chronic airway inflammatory disease. MicroRNAs are shown to be involved in the regulation of inflammation. We investigated the role of microRNA-29b (miR-29b) in the airway inflammation in COPD. The expression of miR-29b in the lung and plasma was examined. The target of miR-29b, bromodomain protein 4 (BRD4), was predicted by online algorithms and verified in human bronchial epithelial (HBE) cells. The expression of BRD4, interleukin (IL)-8, and IL-6 in the lung was also examined. The role of miR-29b in the inflammatory cytokine expression of airway epithelial cells was studied using an in vitro model system. In total, 60 subjects were recruited, including 10 nonsmokers, 24 smokers, and 26 patients with COPD. Both lung and plasma miR-29b are decreased in patients with COPD, and miR-29b expression levels are correlated with pulmonary function and inflammation. BRD4 is increased in the lung of patients with COPD and is correlated with miR-29b and IL-8 expression. miR-29b regulates cigarette smoke extract (CSE)-induced IL-8 expression by targeting BRD4 in HBE cells. The antioxidant N-acetylcysteine prevents CSE-induced miR-29b downregulation and BRD4 and IL-8 upregulation. Our findings indicate that miR-29b may participate in the airway inflammation in COPD by regulating inflammatory cytokine expression through targeting BRD4, plasma miR-29b may serve as a biomarker for disease severity in COPD, and oxidative stress may contribute to the decrease of miR-29b induced by cigarette smoke.

G-Protein-Coupled Estrogen Receptor Antagonist G15 Decreases Estrogen-Induced Development of Non-Small Cell Lung Cancer.

G-protein-coupled estrogen receptor (GPER) was found to promote non-small cell lung cancer (NSCLC) by estrogen, indicating the potential necessity of inhibiting GPER by a selective antagonist. This study was performed to elucidate the function of GPER-selective inhibitor G15 in NSCLC development. Cytoplasmic GPER (cGPER) and nuclear GPER (nGPER) were detected by immunohistochemical analysis in NSCLC samples. The relation of GPER and estrogen receptor ß (ERß) expression and correlation between GPER, ERß, and clinical factors were analyzed. The effects of activating GPER and function of G15 were analyzed in the proliferation of A549 and H1793 cell lines and development of urethane-induced adenocarcinoma. Overexpression of cGPER and nGPER was detected in 80.49% (120/150) and 52.00% (78/150) of the NSCLC samples. High expression of GPER was related with higher stages, poorer differentiation, and high expression of ERß. The protein level of GPER in the A549 and H1793 cell lines was increased by treatment with E2, G1 (GPER agonist), or fulvestrant (Ful; ERß antagonist) and decreased by G15. Administration with G15 reversed the E2- or G1-induced cell growth by inhibiting GPER. In urethane-induced adenocarcinoma mice, the number of tumor nodules and tumor index increased in the E2 or G1 group and decreased by treatment with G15. These findings demonstrate that using G15 to block GPER signaling may be considered as a new therapeutic target in NSCLC.

Pentraxin levels in non-eosinophilic versus eosinophilic asthma.

BACKGROUND: Innate immunity has been thought to be involved in asthma pathogenesis. Pentraxins, acting as soluble pattern recognition molecules, play an important role in humoral innate immunity. Asthma is a heterogeneous inflammatory disease of airways and can be classified as eosinophilic or non-eosinophilic asthma. OBJECTIVE: To investigate whether pentraxin levels differ in subjects with eosinophilic versus non-eosinophilic asthma. Furthermore, to access the predictive performance of pentraxin levels for discriminating asthma inflammatory phenotypes. METHODS: A total of 80 asthmatic patients and 24 healthy control subjects underwent sputum induction at study inclusion. Differential leucocyte counts were performed on selected sputum. Plasma C-reactive protein (CRP), serum amyloid P (SAP), pentraxin 3 (PTX3), and sputum SAP, PTX3, IL-8 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Subjects with non-eosinophilic asthma had significantly increased pentraxin levels compared with those with eosinophilic asthma and healthy controls, with median (interquartile range) plasma CRP levels of 0.86 (0.28-2.07), 0.26 (0.14-0.85), and 0.15 (0.09-0.45)mg/L (P < .001), respectively, plasma SAP levels of 33.69 (19.79-58.39), 19.76 (16.11-30.58), and 20.06 (15.68-31.11)mg/L (P = .003), respectively, and sputum PTX3 levels of 4.9 (1.35-18.72), 0.87 (0.30-2.07), and 1.08 (0.31-4.32)ng/mL (P < .001), respectively. Conversely, sputum SAP concentrations of eosinophilic asthmatics (median, 21.49 ng/mL; IQR, 6.86-38.79 ng/mL) were significantly higher than those of non-eosinophilic patients (median, 8.15 ng/mL; IQR, 2.82-18.01 ng/mL) and healthy controls (median, 8.79 ng/mL; IQR, 2.00-16.18 ng/mL). Asthma patients with high plasma CRP (P = .004), SAP (P = .005) and sputum PTX3 levels (P < 0.001) also had significantly lower sputum eosinophil percentages. Sputum PTX3 levels had the best power (11.18-fold, P < .001) to predict non-eosinophilic airway inflammation in asthma patients. CONCLUSION AND CLINICAL RELEVANCE: Pentraxin levels differed significantly between patients with non-eosinophilic asthma and those with eosinophilic asthma. Furthermore, elevated pentraxin expressions may predict non-eosinophilic airway inflammation in asthmatic patients.

Assessing the effectiveness of problem-based learning in physical diagnostics education in China: a meta-analysis.

Problem-based learning (PBL) has been extensively applied as an experimental educational method in Chinese medical schools over the past decade. A meta-analysis was performed to assess the effectiveness of PBL on students' learning outcomes in physical diagnostics education. Related databases were searched for eligible studies evaluating the effects of PBL compared to traditional teaching on students' knowledge and/or skill scores of physical diagnostics. Standardized mean difference (SMD) with 95% confidence interval (CI) was estimated. Thirteen studies with a total of 2086 medical students were included in this meta-analysis. All of these studies provided usable data on knowledge scores, and the pooled analysis showed a significant difference in favor of PBL compared to the traditional teaching (SMD = 0.76, 95%CI = 0.33-1.19). Ten studies provided usable data on skill scores, and a significant difference in favor of PBL was also observed (SMD = 1.46, 95%CI = 0.89-2.02). Statistically similar results were obtained in the sensitivity analysis, and there was no significant evidence of publication bias. These results suggested that PBL in physical diagnostics education in China appeared to be more effective than traditional teaching method in improving knowledge and skills.

MBL2 polymorphisms and the risk of asthma: A meta-analysis.

BACKGROUND: The association between MBL2 gene polymorphisms and the risk of asthma has been evaluated in multiple studies; however, the results are inconsistent. OBJECTIVE: To perform a meta-analysis to explore whether MBL2 gene polymorphisms were associated with the risk of asthma. METHODS: We searched PubMed, Web of Science, and Cochrane Library to find relevant articles published up to March 2016. Nine studies, including 2066 cases and 2183 controls, were included in the meta-analysis. The strength of association was evaluated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: The results reveal that MBL2 gene polymorphisms (codon 54 A/B, -550 H/L or -221 X/Y) were not associated with the risk of asthma (codon 54 A/B: BB+AB vs AA: OR, 1.02; 95% CI, 0.85-1.23; -550 H/L: LL+HL vs HH: OR, 0.81; 95% CI, 0.63-1.03; -221 X/Y: XX+YX vs YY: OR, 0.85; 95% CI, 0.69-1.04). Subgroup analysis by ethnicity implied that the MBL2 codon 54 A/B polymorphism was not significantly associated with the risk of asthma in Asians (BB+AB vs AA: OR, 0.95; 95% CI, 0.70-1.29) or whites (BB+AB vs AA: OR, 1.07; 95% CI, 0.84-1.35). CONCLUSION: The results indicated that MBL2 gene polymorphisms (codon 54 A/B, -550 H/L or -221 X/Y) may be not associated with the risk of asthma.

Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1ß and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia.

Pseudomonas aeruginosa causes hospital-acquired pneumonia and is associated with high mortality. An effective response to such an infection includes efficient clearance of pathogenic organisms while limiting collateral damage from the host inflammatory response, known as host resistance and host tolerance, respectively. P. aeruginosa expresses a type III secretion system (T3SS) needle complex that induces NLRC4 (NOD-like receptor C4) activation, interleukin-1ß (IL-1ß) production, and host tissue damage. Chitinase 3-like-1 (Chil1) is expressed during infection and binds to its receptor, IL-13 receptor α2 (IL-13Rα2), to regulate the pathogen-host response during Streptococcus pneumoniae infection, but the role Chil1 plays in balancing the host resistance and host tolerance during P. aeruginosa pneumonia is not known. We conducted experiments using C57BL/6 mice with or without a genetic deficiency of Chil1 and demonstrated that Chil1-deficient mice succumb to P. aeruginosa infection more rapidly than the wild type (WT). The decreased survival time in infected Chil1-deficient mice is associated with more neutrophils recruited to the airways, more lung parenchymal damage, and increased pulmonary consolidation while maintaining equivalent bacterial killing compared to WT mice. Infected Chil1-deficient mice and bone marrow-derived macrophages (BMDMs) from Chil1-deficient mice have increased production of tumor necrosis factor alpha (TNF-α) and IL-1ß compared to infected WT mice and macrophages. Infection of Chil1-deficient BMDMs with non-NLRC4-triggering P. aeruginosa, which is deficient in the T3SS needle complex, did not alter the excessive IL-1ß production compared to BMDMs from WT mice. The addition of recombinant Chil1 decreases the excessive IL-1ß production but only partially rescues stimulated BMDMs from IL-13Rα2-deficient mice. Our data provide mechanistic insights into how Chil1 regulates P. aeruginosa-induced host responses.

Impact of village-based health education of tobacco control on the current smoking rate in Chinese rural areas.

The number of smokers in Chinese rural areas is more than 200 million, which is twice that in cities. It is very significant to carry out tobacco control interventions in rural areas. We performed this community intervention study to evaluate the efficacy of village-based health education of tobacco control on the male current smoking rate in rural areas. The population of this study was the males above 15 years old from 6 villages in rural areas. The villages were randomly assigned to intervention group or control group (3 villages in each group). Self-designed smoking questionnaire was applied. The intervention group received the village-based health education of tobacco control for one year. The primary outcome measurement was the male current smoking rate. In the baseline investigation, completed surveys were returned by 814 male residents from the control group and 831 male residents from the intervention group. The male current smoking rate in the control group and the intervention group was 61.2% and 58.5%, respectively, before intervention. There was no significant difference between these two groups (P>0.05). After one-year intervention, the current smoking rate in the intervention group (51.2%) was significantly lower than that in the control group (62.8%) (P<0.001). Our study suggested that the village-based health education of tobacco control was effective in lowering the male current smoking rate in rural areas, which could be a suitable and feasible way for tobacco control in the Chinese rural areas.